The overall objective of this Program Project Grant is to study the regulation of the circulation in pathological states. The program represents the coordinated effort of several investigators in clinical and in basic science specialties to study in a systematic way mechanisms of vascular properties as well as cardiovascular control in hypertension, myocardial ischemia, heart failure and abnormal circulatory states. The approach to the work will include studies on cultured vascular cells, isolated vessels, animal models of disease, normal human subjects and patients. Each investigator will apply his special expertise in the laboratory to the solution of specific problems and the interaction between all investigators will continue to provide the appropriate environment for the emergence of new ideas and new directions for research. The program deals primarily with cardiovascular control mechanisms in physiologic and pathophysiologic states with emphasis on neurohumoral and renal factors in hypertension and heart failure; on factors which determine myocardial perfusion during ischemia and mechanical stress factors. In the area of cellular mechanisms, the mechanisms of increased reactivity of arterial muscle in hypertensive animal models are examined with respect to the role of electrophysiologic and neurotropic factors. Fundamental studies on the biochemical determinants of muscular contraction in vascular and cardiac muscle will be carried out. Core resources and facilities provide cohesive support for this interdisciplinary program.